Lymphocyte Signalling Explained

The primary goals of the immune system are to protect the body against invading pathogens and prevent subsequent infection. This powerful system must be carefully balanced to ensure that it does not destroy the body it has evolved to protect.

Lymphocytes are white blood cells important for protecting the body from disease by stimulating immune responses and retaining a memory of prior infections. We aim to understand the processes that regulate the development, survival and function of these cells.

Immune Cell Development

We have identified genes responsible for regulating lymphocyte development and will uncover the
mechanisms by which the protein product of these genes function to allow the cells to mature and survive during the life-course.

Using a variety of approaches, including cutting-edge technology developed at the Institute, we will uncover the role of the PI3K enzymes in lymphocyte
development. Proteins called GIMAPs are expressed in lymphocytes and influence how long they persist in the body. By identifying where GIMAPs are located within the cell, and the proteins with which they interact, we will build an understanding of their role in immunology. Controlling the rate at which proteins are made in the cell is critically important in lymphocyte development. We seek to determine the mechanism of action for a number of these important control steps.

Immune Responses to the Environment.

Controlling the microbial population on exposed surfaces such as the skin, gut and lung is a delicate problem for the immune system. It must balance the need to remove harmful microorganisms without compromising organ function. This is essential to ensure lasting health and well-being. The skin, gut and lung contain a diverse mix of immune cells, each with individual functions. We examine how these cells interact with each other and with the microbial populations at these sites.

Furthermore, we identify how environmental stimuli affect lymphocyte function and immunological memory. B lymphocytes (B cells) provide a specialised response to infection by identifying specific pathogens. They then initiate a series of gene expression changes resulting in the production of antibodies that stick to the pathogen, blocking entry into cells and helping other immune cells recognise and destroy it. This process results in an ‘immunological memory’, which is the basis for how vaccines work. Using state-of-the-art laboratory and computational methods we identify how B cell development and the production of protective antibodies is regulated.

We have found that PI3K is necessary to ensure that the immune system works in a concerted manner in response to infection and will identify how it and other proteins are employed by vaccines to generate immunity.